DNA methylation in the apolipoprotein-A1 gene is associated with episodic memory performance in healthy older individuals

Lazarus, Jessica, Mather, Karen A., Armstrong, Nicola J., Song, Fei, Poljak, Anne, Thalamuthu, Anbupalam, Lee, Teresa, Kochan, Nicole A., Brodaty, Henry, Wright, Margaret J., Ames, David, Sachdev, Perminder S. and Kwok, John B. J. (2015) DNA methylation in the apolipoprotein-A1 gene is associated with episodic memory performance in healthy older individuals. Journal of Alzheimer's Disease, 44 1: 175-182. doi:10.3233/JAD-141314

Author Lazarus, Jessica
Mather, Karen A.
Armstrong, Nicola J.
Song, Fei
Poljak, Anne
Thalamuthu, Anbupalam
Lee, Teresa
Kochan, Nicole A.
Brodaty, Henry
Wright, Margaret J.
Ames, David
Sachdev, Perminder S.
Kwok, John B. J.
Title DNA methylation in the apolipoprotein-A1 gene is associated with episodic memory performance in healthy older individuals
Journal name Journal of Alzheimer's Disease   Check publisher's open access policy
ISSN 1875-8908
Publication date 2015-01-01
Year available 2015
Sub-type Article (original research)
DOI 10.3233/JAD-141314
Open Access Status Not Open Access
Volume 44
Issue 1
Start page 175
End page 182
Total pages 8
Place of publication Amsterdam, Netherlands
Publisher IOS Press
Language eng
Formatted abstract
Background:  DNA methylation variation has been implicated in memory, cognitive performance, and dementia. Plasma apolipoprotein-A1 (ApoA1) levels may act as a biomarker of age-associated cognitive performance and decline.

Objectives:  To estimate the heritability of plasma ApoA1 protein levels; to examine DNA methylation variation within the APOA1 gene; and to investigate whether APOA1 methylation is associated with plasma ApoA1 levels and episodic memory performance.

Method:  Heritability of ApoA1 protein levels in Older Australian Twins Study (OATS) was assessed using structural equation modelling. APOA1 methylation levels were assayed in two cohorts of cognitively normal older individuals. The methylation status of 12 CpGs in 24 twin pairs from OATS was assayed using the Illumina 450K methylation array. Candidate CpGs were assayed in 454 individuals from Sydney Memory and Ageing Study (Sydney MAS) using pyrosequencing. Regression analyses assessed associations between APOA1 methylation levels, ApoA1 plasma levels, and memory performance.

Results:  No significant heritability was observed for ApoA1 protein levels. APOA1 candidate-gene analyses revealed CpG sites associated with memory performance in the twin study (p < 0.050). Replication of an association between methylation of a specific CpG (cg03010018) in APOA1 and memory performance was observed in Sydney MAS (β = −0.145, p = 0.010). Methylation of this CpG site was also significantly correlated with ApoA1 protein levels (β = 0.161, p = 0.019). However, no relationship between a composite memory domain score and methylation was observed (p = 0.389).

Conclusion:  Findings demonstrated that epigenetic control of APOA1 expression and DNA methylation levels are associated with episodic memory performance in older adults.
Keyword Aging
Apolipoprotein A1
DNA methylation
Episodic memory
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 401162
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
School of Medicine Publications
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